The present invention relates to new 13-thiaprostaglandin intermediates which are exceptionally valuable for the stereospecific preparation of 13-thiaprostaglandin derivatives. It also relates to their preparation and use for the preparation of known 13-thiaprostaglandin derivatives. Moreover, the invention relates to a new process for the preparation of known 13-thiaprostaglandin derivatives, starting from the new intermediates.
13-Thiaprostaglandin derivatives are known from German Offenlegungsschrift Nos. 2,256,537, 2,422,924 and U.S. Ser. No. 096,348, filed on Nov. 21, 1979, corresponding to German Offenlegungsschrift No. 2,644,972, and possess valuable pharmacological properties. In this regard, the disclosures of all of these references are incorporated by reference herein. These 13-thiaprostaglandin derivatives, for example, in particular those of the E type, have a hypotensive action. This action is evident, for example, on administration, by continuous infusion, to cats narcotized with barbiturate. In this test, the arterial blood pressure is recorded kymographically. The test substances are infused in aqueous propylene glycol solution over a period of 10 minutes.
Moreover, the 13-thiaprostaglandin derivatives have vasodilative, antiphlogistic, diuretic and bronchial spasm-relieving properties; inhibitory effects on the secretion of gastric juice, the aggregation of thrombocytes, the degradation of lipids and the release of noradrenalin; and also nasal decongestant properties. These can likewise be established by fully conventional methods.
The 13-thiaprostaglandin derivatives can also influence the function of the corpus luteum, the transfer of ova through the fallopian tubes, nidation and fertility. Thus, these 13-thiaprostaglandin derivatives, in particular those of the F type, show an oestrus-synchronizing action, for example in cattle, horses, sheep, pigs and dogs. In order to utilize this action, the active compound is injected intramuscularly, advantageously between the 7th day and the 12th day of the cycle.
Several processes for the preparation of these 13thiaprostaglandin derivatives are known, but they have certain disadvantages. The yields are not always satisfactory, the syntheses proceed via a large number of reaction steps, the work-up is difficult and the purity of the resulting products leaves something to be desired. In particular, in synthesizing these 13-thiaprostaglandin derivatives, which is difficult because of the complex stereochemistry involved, there is a need for processes which lead to isomerically and epimerically pure products in a few reaction steps.